Search Results (172)

Seismic-resistant reinforcing steels play a key role in structures subjected to earthquake loading, requiring an optimal balance between strength, ductility, and weldability. Microalloying with vanadium (V), niobium (Nb), and titanium (Ti) is widely used to improve these properties through precipitation strengthening and grain refinement. This work aims to contribute to the development of seismic-resistant reinforcing steels for the Moroccan construction sector. A literature review identified key international requirements, including a tensile-to-yield strength ratio (Rm/Re) of 1.15–1.35 and a total elongation at maximum force (Agt ≥ 7%). In parallel, Moroccan reinforcing bars were mechanically and microstructurally characterized. A conventional steel containing 0.65 wt.% Mn and no vanadium was used as a reference. This steel exhibited limited strain-hardening capacity, with Rm/Re ratios between 1.12 and 1.15. To improve this behavior, steels containing 1.1 wt.% Mn with different vanadium additions were investigated. Preliminary results indicate that vanadium microalloying improves mechanical performance through combined precipitation strengthening and ferrite grain refinement. The increase in strength is likely associated with fine V(C,N) precipitates formed during cooling, while ferrite grain refinement appears to contribute to maintaining ductility. This synergistic effect results in a more favorable strength–ductility balance, supporting the development of seismic-resistant reinforcing steels for structural applications. Full article

Background/Objectives: Precision nutrition informed by genetic profiling has been proposed to improve public health outcomes; however, long-term, community-based evidence remains limited. This study evaluated the long-term health and economic impacts of the Sakado Folate Project. Methods: Since 2006, residents participating in the Sakado Folate Project received gene-guided nutritional counseling focused on folate intake and related lifestyle factors. Target genes included methylenetetrahydrofolate reductase (MTHFR), angiotensinogen (AGT), adrenoreceptor B3 (ADRB3), and uncoupling protein 1 (UCP1); Δ5-fatty acid desaturase (FADS1) was incorporated later. Biochemical markers, genetic polymorphisms, and health indicators were monitored longitudinally. Population-level health outcomes and per-capita medical expenditure data were compared with regional and national statistics. Results: In program participants (n = 888), folate status and biochemical indicators improved: 76.1% achieved the serum folate target (≥9.5 ng/mL) and 55.3% achieved the serum total homocysteine target (≤7 μmol/L). Healthier lifestyle behaviors were observed across 99,565 Sakado residents, with the city recording the highest proportion of individuals actively attempting lifestyle improvement (31%) of all districts in the region. Disease prevalence was lower in Sakado City than in Saitama Prefecture overall, at standardized prevalence ratios of 52% for stroke and 86% for cerebral infarction. Per-capita medical expenditure was also lower in Sakado City (¥337,800) than the national average (¥392,044) in 2021. Conclusions: Long-term implementation of a community-based, gene-guided nutritional intervention may improve population health outcomes and reduce healthcare expenditures. Integrating nutrigenomics into public health strategies alongside community education and food environment improvements may contribute to sustainable healthcare systems in aging societies. Full article

Background/Objectives: While the functions of angiotensin-converting enzyme (ACE) 1 and 2 are well established in peripheral tissues, the role of the spinal ACE1 and ACE2 pathways in the development of neuropathic pain remains unclear. This study examined the role of the spinal ACE1 and ACE2 pathways in trigeminal neuropathic pain produced by inferior alveolar nerve (IAN) injury. Methods: The experiments were conducted using male Sprague-Dawley rats (6–8 weeks old, weighing 220–250 g). The left mandibular second molar was extracted, and a dental mini-implant was placed to induce IAN injury. IAN injury produced robust and long-lasting mechanical allodynia and markedly increased angiotensinogen (AGT) expression within the ipsilateral trigeminal subnucleus caudalis (iTSC). Results: Neuropathic mechanical allodynia was inhibited by intracisternally administered losartan (an angiotensin II type-1 receptor antagonist), but not by an angiotensin II type-2 receptor antagonist. Intracisternal treatment with captopril (an ACE1 inhibitor) and diminazene aceturate (an ACE2 activator) produced significant anti-allodynic effects. Intracisternally injected angiotensin-(1-7) reduced neuropathic mechanical allodynia, and this anti-allodynic effect was blocked by pretreatment with A779, a Mas receptor inhibitor. In naïve rats, the intracisternal administration of DX600 (an ACE2 inhibitor) resulted in mechanical allodynia, which was inhibited by intracisternal pretreatment with losartan. IAN injury led to upregulated ACE1 expression and downregulated ACE2 expression in the iTSC. Conclusions: Our findings indicate that IAN injury induces a polarized shift in the ACEs within the iTSC, characterized by increased ACE1 and decreased ACE2 expression. Their modulation may therefore offer a promising strategy for developing effective treatments for chronic pain. Full article

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder resulting from mutations in the alanine–glyoxylate aminotransferase (AGXT) gene, leading to excessive systemic deposition of calcium oxalate. This condition is an important cause of end-stage renal disease in children and poses a serious threat to patient survival. Current therapeutic approaches are limited primarily to conservative management and organ transplantation, underscoring the need for more effective treatments. Gene replacement therapy represents a promising alternative strategy. In this study, Agxt⁻/⁻ mice lacking exons 3–8 were characterized, confirming the complete loss of hepatic alanine–glyoxylate aminotransferase (AGT) expression and the presence of early-onset hyperoxaluria. Exposure to glyoxylic acid induced pronounced renal calcium oxalate crystal deposition, establishing a robust and previously unreported induction approach in gene-edited PH1 mouse models. Using this platform, human AGXT cDNA was delivered via the liver-tropic, low-immunogenic AAV843 vector, which has been employed in clinical trials for hemophilia. Gene therapy resulted in normalization of urinary oxalate levels, restoration of hepatic AGT expression, and significant attenuation of renal injury and nephrocalcinosis. These therapeutic effects were accompanied by significant suppression of key mediators involved in renal inflammation, necroptosis, and fibrosis. Moreover, transgene expression was highly specific to the liver and was not associated with hepatotoxicity. These results demonstrate that AAV843-mediated AGXT gene replacement is a safe and effective approach that achieves phenotypic correction in a murine model of PH1, warranting further evaluation in preclinical studies. Full article

Anaerobic germination tolerance (AGT) is a critical adaptive trait for rice establishment in flood-prone environments and direct-seeded systems. Here, we identified and validated the quantitative trait locus qAG2.1 for AGT and introgressed it into the elite lowland rice variety CR Dhan 801 through marker-assisted backcross breeding. The introgressed lines exhibited significantly improved germination under anaerobic conditions, demonstrating the effectiveness of qAG2.1 in a high-yielding genetic background. While CR Dhan 801 showed a low anaerobic germination percentage (17.6%), the donor ARC10424 exhibited 82.6%, and the best-performing introgressed line (22009-3) achieved 49.2%. Importantly, the improved lines maintained agronomic performance comparable to CR Dhan 801 under non-stress conditions, indicating minimal yield penalty. To gain mechanistic insight, the qAG2.1 interval was dissected in silico to prioritise candidate genes putatively associated with AGT. This analysis highlighted genes linked to ethylene biosynthesis and signalling (e.g., OsACO3, OsERF109), abscisic acid biosynthesis (OsNCED1), gibberellin homeostasis (OsGA2ox9), trehalose metabolism (OsTPS5, OsTPP1), detoxification of anaerobic by-products (OsALDH2A), and water transport (OsPIP1;3). Collectively, these results validate qAG2.1 as a further deployable locus for improving anaerobic germination in elite rice backgrounds and provide a set of putative candidate genes for future functional characterisation. Full article

Pre-eclampsia is a Hypertensive Disorder of Pregnancy (HDP) characterized by hypertension and proteinuria, affecting 2–8% of pregnancies worldwide and constituting a major public health concern. Genes of the renin–angiotensin system have been investigated as potential causative factors, but inconclusive results have been obtained. The objective of this pilot study is to evaluate the possible contribution of alleles, genotypes or haplotypes of two single-nucleotide polymorphisms (SNPs) T174M (rs4762) and M235T (rs699) in AGT gene to pre-eclampsia in the Mexican population. We analyzed the association by performing PCR-RFLP with DNA extracted from whole blood samples of Mexican women with pre-eclampsia or normotensive pregnancy and the general population (GP). Our results showed a significant difference in the rate of heterozygosity for the T174M polymorphism between cases and controls. In addition, this polymorphism together with homozygosity for the M235T polymorphism may represent a possible genetic marker associated with pre-eclampsia. The T-C haplotype (174M–M235) was more common in patients with pre-eclampsia (non-significant difference p = 0.0503). The identification of genetic risk markers may support the early detection of pre-eclampsia and strengthen peripartum maternal health strategies within a global health framework aimed at reducing maternal mortality. Full article

Primary hyperoxalurias (PHs) are rare autosomal recessive disorders characterized by overproduction of oxalate, a metabolic end product that readily forms calcium oxalate crystals. Excess hepatic oxalate leads to recurrent kidney stones, nephrocalcinosis, and progressive renal injury, often culminating in end-stage kidney disease (ESKD). Once renal clearance declines, systemic oxalate accumulation can cause multisystem deposition. PH encompasses three types—PH1, PH2, and PH3—caused by deficiencies in the hepatic enzymes AGT, GRHPR, and HOGA1, respectively, resulting in accumulation of glyoxylate and subsequent oxalate overproduction. Clinical presentation varies from infantile oxalosis to adult-onset recurrent nephrolithiasis, with PH1 generally being the most severe. Diagnosis relies on urinary oxalate measurements, plasma oxalate in advanced chronic kidney disease, urinary metabolite profiling, imaging, and genetic testing. Management includes hyperhydration, citrate supplementation, pyridoxine for responsive PH1 patients, dialysis and transplantation when required, while RNA interference therapies targeting glycolate oxidase or LDHA have demonstrated substantial biochemical efficacy in PH1 and represent promising emerging therapeutic options, although long-term clinical outcome data remain limited and broader applicability to other PH types is still under investigation. Future strategies focus on modulating intestinal oxalate absorption, gut microbiome therapies, oxalate-degrading enzymes, and novel gene-editing approaches. Early diagnosis and individualized management are critical to prevent kidney injury and systemic oxalosis. In this review, we summarize the genetic, biochemical, and clinical features of PH and discuss current and emerging therapeutic strategies. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Vasculitides are a heterogeneous group of disorders characterized by inflammation of blood vessel walls, leading to tissue ischemia and organ injury. Traditional inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used but lack diagnostic specificity. This has driven the search for more informative biomarkers across vasculitis subtypes. This review summarizes current evidence for validated and emerging biomarkers in large-, medium-, small-, and variable-vessel vasculitis, as well as single-organ vasculitis. Key analytes reflect systemic inflammation, such as serum amyloid A (SAA) and interleukin-6 (IL-6), as well as endothelial activation, complement pathways, neutrophil and macrophage activation, and organ-specific damage. Promising candidates include pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9) in large-vessel vasculitis; N-terminal pro-B-type natriuretic peptide (NT-proBNP) and S100 proteins in Kawasaki disease; galactose-deficient immunoglobulin A1 (Gd-IgA1) and urinary angiotensinogen (AGT) in IgA vasculitis; and tissue inhibitor of metalloproteinases-1 (TIMP-1), S100 proteins, complement C3, and PTX3 in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although these biomarkers provide mechanistic insight, most lack disease-specificity, external validation, or standardized assays. Future progress will require multicenter studies, harmonized testing, and integrated biomarker panels combined with imaging modalities to improve diagnosis, activity assessment, and monitoring. Full article

Introduction: The aim of this study was to determine the position of otoconial debris in lateral ampullar or non-ampullar canalolithiasis, based on two parameters: (1) the direction of the nystagmus appearing when the patient lies down, if present, and (2) the positional nystagmus evoked by the supine roll test. Methods: Theoretical results were compared with a population of 170 patients observed over the past ten years for horizontal canal benign paroxysmal positional vertigo (HC-BPPV). The series included 141 geotropic and 29 apogeotropic cases. Results: Among the geotropic forms, 80 showed no supine nystagmus (Geotropic Nystagmus with no supine nystagmus, GT0) (56.7%), 51 had supine nystagmus directed toward the healthy side (Geotropic Nystagmus with supine nystagmus congruent, direct toward the healthy side, GT+) (36.2%), and 10 toward the affected side (Geotropic Nystagmus with supine nystagmus incongruent direct to the affected side, GT−) (7.1%). In the apogeotropic group, 10 showed no supine nystagmus (Apogeotropic nystagmus with no supine nystagmus, AGT0) (34.6%), 16 had nystagmus toward the affected side (Apogeotropic Nystagmus with supine nystagmus congruent, direct toward the affected side, AGT+) (55.2%), and 1 toward the healthy side (Apogeotropic Nystagmus with supine nystagmus Incongruent, direct toward the healthy side, AGT−) (3.4%). Two cases presented monopositional apogeotropic nystagmus (mAGT), consistent with a “sieve-type canal jam” (6.8%). Overall, 90 out of 170 patients (52.9%) showed no nystagmus in the supine position, with a statistically significant difference between variants (p = 0.0474, Yates correction). Conclusions: The comparison between lying-down nystagmus and positional nystagmus, assessed through the Supine Roll Test as the leading diagnostic maneuver for horizontal canal involvement, may help identify the initial location of debris within the lateral semicircular canal and guide the appropriate liberatory maneuver, while the effectiveness and side of the maneuver allow the distinction between canal-side and utricular-side jams. Full article

Background: Recurrent pregnancy loss (RPL) is a multifactorial condition in which genetic variants associated with thrombophilia may contribute to altered coagulation and adverse pregnancy outcomes. Objective: This study aimed to investigate the association between thrombophilia-related single nucleotide variants (SNVs) and coagulation-related metabolites in a cohort of Mexican women with RPL. Methods: A retrospective and descriptive design was conducted including 105 women with at least two consecutive miscarriages and with a multidisciplinary approach that included a thrombophilia-associated SNVs panel. Peripheral blood samples were collected after fasting for biochemical and molecular analyses. Genotyping of thrombophilia-associated SNVs was performed using real-time PCR with custom-designed TaqMan probes on a Rotor-Gene Q platform, including variants in AGT (rs4762, rs699), F7 (rs6046), FGB (rs1800790), MTR (rs1805087), MTRR (rs1801394), MTHFR (rs1801133, rs1801131), F2 (rs1799963), F5 (rs6025), SERPINE1 (rs1799889), F12 (rs1801020), and F13A1 (rs5985) genes. Coagulation parameters evaluated were folic acid, cobalamin, fibrinogen, D-dimer, homocysteine, antithrombin III activity, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and Factor XII activity. Results: Significant differences were found in INR values across F7-rs6046 genotypes (p = 0.006), with an additive model showing a mean difference of 0.05 (p = 0.0009). The F12-rs1801020 variant was strongly associated with Factor XII activity (p = 0.002) and aPTT (p = 0.045). Conclusions: These findings indicate that F7-rs6046 and F12-rs1801020 genotypes influence specific coagulation parameters, suggesting that certain thrombophilia-associated SNVs may modulate the hemostatic profile in Mexican women with RPL and contribute to personalized risk assessment in reproductive medicine. Full article

Background/Objectives: Pathogenic variants in the GBA1 gene, which encodes the lysosomal enzyme $\beta$-glucocerebrosidase, cause Gaucher disease (GD) and represent one of the strongest genetic risk factors for Parkinson’s disease (PD). However, not all carriers develop PD, suggesting the involvement of additional modifiers. Transcriptomic alterations shared between GD and PD may reveal such modifiers and provide insights into the mechanisms linking GBA1 to PD. Methods: Eighteen transcriptomic datasets spanning GD, GBA1-associated PD, and sporadic PD were integrated to identify shared, directionally concordant differentially expressed genes, followed by pathway enrichment analysis. Causal relationships were assessed using two-sample Mendelian randomisation with whole-blood and brain genetic instruments and PD GWAS summary statistics. Diagnostic relevance was evaluated in independent datasets using machine learning, while metabolic implications were explored with a neuron-specific genome-scale metabolic model. Results: Shared DEGs were enriched in lysosomal, lipid, redox, and endocrine pathways. Mendelian randomisation prioritised 12 risk genes in whole blood and 5 in brain tissue, with 4 overlapping; risk-increasing effects were observed for GPNMB, MMP9, TRIM22, TESMIN, NFE2L3, FAM89A, METTL7A, PID1, NECAB2, and LPL, whereas GIPR and RASGRF2 showed protective effects, and AGT was brain-specific. Diagnostic signals were concentrated in a subset of genes, while metabolic modelling revealed convergent but subtype-specific perturbations across metabolic circuits. Conclusions: Convergent genetic, transcriptomic, and metabolic evidence supports at least two mechanistic routes to PD risk: a GBA1-sensitised lysosomal–lipid/redox axis, and a GBA1-independent neuronal–endocrine axis. These findings explain the variable risk among GBA1 carriers, identify candidate biomarkers, and highlight pathway-anchored targets for stratified intervention. Full article

Endometrial cancers increase expression of the renin–angiotensin system (RAS). This study aimed to determine if inhibiting the RAS would reduce the viability and proliferation of endometrial cancer cells. The expression of RAS genes was measured in three endometrial epithelial adenocarcinoma cell lines (Ishikawa, HEC-1-A, AN3CA). Ishikawa cells had the highest expression of REN, ACE, and AGTR1 mRNA. AGT mRNA and protein levels were most abundant in HEC-1-A cells. We then determined the effects of drugs that inhibit the action of renin (VTP-27999 and aliskiren) or angiotensin-converting enzyme (perindoprilat) or block the angiotensin II type 1 receptor (losartan and telmisartan). Overall, VTP-27999, aliskiren, perindoprilat, and losartan had minimal effects on cell viability in all three cell lines, and combinations of these drugs did not have any effect. Telmisartan (a dual angiotensin receptor blocker and PPAR-γ agonist) significantly reduced the viability of all three cell lines and reduced the proliferation of both Ishikawa and AN3CA cells. Telmisartan was more effective than troglitazone (PPAR-γ agonist) in Ishikawa and HEC-1-A cells. RAS inhibitors were most effective in Ishikawa cells, which had the highest levels of RAS expression. Therefore, levels of RAS expression in endometrial cancers might indicate the potential efficacy of RAS drugs. Full article

Athletic performance results from complex interactions between genetic and environmental factors. This review compiles and synthesizes available literature on polymorphic genes associated with endurance, power, and strength performance, as well as their links to injury susceptibility and chronic metabolic diseases. Endurance performance is modulated by ACE, PPARGC1A, HFE, UCP2, UCP3, CDKN1A, and PPARA, regulating mitochondrial biogenesis, oxygen utilization, and muscle fiber composition. Power performance involves ACTN3, MCT1, IGF1, AMPD1, AGT, and AGTR2, affecting anaerobic metabolism, lactate clearance, and fast-twitch fiber recruitment. Strength performance is influenced by AR, PPARG, ARK2N, MMS22L, LRPPRC, PHACTR1, and MTHFR, related to androgen signaling, muscle hypertrophy, and recovery. Injury-related genes (COL1A1, COL5A1, IL6, VEGFA, NOG) and metabolic risk genes (FTO, PPARG, ADRB3) further highlight the clinical relevance of genomics. Collectively, these insights support the application of genetic information to personalize training, enhance performance, prevent injuries, and guide exercise interventions to mitigate metabolic disease risk. Full article

This study investigates the mechanical properties of titanium (Titanflex®) and cobalt-chromium (Co-Cr) alloys for potential use in removable denture bases. Titanium alloys have gained attention due to their biocompatibility and regulatory concerns surrounding Co-Cr, which has been classified as a carcinogenic, mutagenic, and toxic to reproduction (CMR) substance under EU MDR (2017/745). Using selective laser melting (SLM), test specimens of Titanflex® and Co-Cr alloys were 3D-printed at different angles (0°, 45°, 90°) and compared to conventionally cast Co-Cr samples. Tensile testing was conducted to assess modulus of elasticity (E), proof stress (Rp_0.2), ultimate tensile strength (Rm), elongation parameters (Ag, Agt, At), and maximum load (Fm). Results showed that Titanflex® printed at 45° (Ti45) exhibited the highest Rp_0.2, Rm, and Fm, indicating superior strength and plastic resistance. Ti0 displayed the greatest elongation properties, highlighting titanium’s ductility. Co-Cr alloys demonstrated higher stiffness but lower ductility. Printing orientation significantly influenced mechanical properties, particularly in 3D-printed samples. Overall, Ti45 presented a balanced profile of strength and flexibility, making it a promising candidate for denture bases, while Co-Cr remains a rigid alternative with established clinical use. Future research should explore long-term performance under functional and biological conditions to guide clinical application. Full article